Sunday, 23 September 2007

Reaction or catalyst? Which started life?

If only the question was as simple as ‘which came first the chicken or the egg’ (answer: the egg). The question here is which came first - DNA or proteins. as we all know DNA stores the code to make proteins but proteins are needed to read this code and make more DNA. Obviously you can’t have one without the other. So the RNA world hypothesis was born. RNA can do both store information and catalyse reactions, perhaps even catalyse its own replication. I believe this is a beautiful theory. However beauty is only skin deep. There are real problems with this explanation of the origins of life apart from the obvious difficulties in testing it, which is true for any explanation of the origin of life. RNA is famous for being chemically unstable. It can break itself down quite easily (especially in alkaline conditions). Also where did the RNA come from? I don’t mean did it come from outer space (because radiation levels in space are so high RNA or cells could not have survived). I mean how the molecules were created on earth. Like it or not RNA is a complex molecule and no experiment trying to recreate the primordial soup has ever found RNA nucleotides. Or any really complex molecules, only the simplest of amino acids have been made.

This has lead to another explanation for the origins of life. Perhaps thinking of life as a bunch of replicators has blinded use to it. Living organisms can also be thought of as chemical factories. Genes and their products are simply there to control these reactions. Some believe it was chemical reactions that came before the proteins or RNA that catalyse the reaction. This is called the metabolism first theory. People who follow this theory have described what is needed for a chemical system to be the beginnings of life. 1) A boundary or form of membrane is needed to keep life and non-life away from each other. The 2nd law of thermodynamics states the universe my decrease in order but life increases in order so inside the boundary entropy decreases but this generates heat that causes an increase in entropy outside it. 2) An energy source must have existed. Perhaps some sort of redox reaction to power the chemical reactions in the metabolism first model. Radiation may have been used. 3) The energy source must be linked to the other chemical reaction. For me this is difficult to see how this could happen without proteins there to help things along but perhaps if I knew more chemistry it would be clearer. We use ATP as our energy currency but how could redox reactions or radiation be linked to these ancient chemical reactions? 4) The chemical reactions must be able to change and evolve. If a cycle of reactions was created where A became B and B became C and C became D and D became A again we have something to expand upon. If we had a carbon input such as E we could take compounds off the cycle and expand it (see diagram). These reactions could be powered by a redox reaction of X to Y. Eventually complex molecules could be created 5) One final requirement for these reactions to have been the origins of life is need and that is to be able to replicate. It is hard to imagine how this is possible before a lipid membrane existed for it to divide into two. If possible this would have allowed for Darwinian evolution through the competition for recourses.

The RNA-first approach has some support for it. Minerals have been found that contain boron in ‘containers’ or ‘bowls’ in Death Valley which could help create the ribose sugar in RNA. If such pores with boron existed billions of years ago RNA could have been created. Laboratory experiments have shown some randomly generated RNA molecules can catalyse the addition of an ATP molecule to itself. This is tested by using an ATP molecule with a sulphur atom not an oxygen atom and using a column that pulls out the sulphur containing RNA molecules only. RNA can carryout many reactions such as making and breaking DNA and RNA links and amide bonds and even make links with sugars. So their is diversity in RNA’s ability to catalyse reactions but its limit appears to be speed. It is possible one reason proteins took over from RNA as life’s catalyst because proteins are faster as well as because protein is more stable. Metabolism first has the great weakness of not having much lab experiments to support it but only computer simulations.

I believe these two theories could work together. Perhaps it is only because I find the rna world aesthetically pleasing i want to save it but these reactions could eventually become so complex they make rna. Over time these built up and started to take control and then made proteins to do much of there job when dna then took over as the info store and rna was simply the messenger and helps out in only a few reactions today. This nicely explains why the formation of the peptide bond in the ribosome is still done by rna. We could go even further into theory and suggest there was a polymer before RNA that could act as catalyse and self replicator. PNA has been suggested. Instead of having the sugar-phosphate backbone like RNA and DNA it has peptides attached to bases forming a backbone. Sadly such a molecule does not exist in our cells today or leave fossils in the ground for us to examine so we cannot test if PNA was really the first molecules that lead to life. If PNA did exist it all became RNA and then DNA.

At the moment we have many ideas about what may have been involved with the start of life on earth but it is difficult to prove anything. What we can do is explore the potentials of these molecules or chemical systems. After all theories about the origins of life cannot be tested directly but the do make predictions and by testing these predictions we can hopefully learn a lot.

References

Albert et al. (2002) Molecular biology of the cell. 4th edition.

Shapiro (2007) A simpler origin for life. Scientific American 296: 24-31.

5 comments:

Because no one else will comment on my post I will! I did not mention LUCA. He is our very great grandparent. In fact of all life. LUCA stands for Last Universal Common Ancestor the first species then diverged into bacteria and the archaea/eukaryote branches of the tree of life! I have recently read some believe membranes evolved after LUCA and he was not cellular life. LUCA came after DNA life. This apparently explains why archaea have very unusual membrane chemistry. But how does this explain why archaea and eukaryotes are different because we shared a common ancestor recently. It seems stupid to me. Complex metabolism such as glycolysis and so on would have arrived before cellular life and I find this hard to believe. Wouldn’t you have needed individuals to compete in a Darwinian fashion to create complex metabolism such as this? And one final thing, membrane proteins are shared by all 3 domains of the tree of life so mush have existed in LUCA and therefore LUCA was cellular life with a membrane! I just thought it was interesting so I shared.

I have just read your post quickly, so I'll need to read it again more carefully before being able to thing about it properly and contribute in some inteligent way to the debate...

However, about the PNA. Am I right in thinking that people are trying to build these DNAs with a peptide bond as some sort of therapy for certain diseases? I think one of the biochemists in my tutorial last term was writing an essay on it... I should probably find out more about it!

You would not believe some of the weird things I have read in newscientist (unless you read them too). Some people believe quantum physics played a role in the origins of life. People are trying to create quantum computers. These will exist in several states at once so can calculate several things at once therefore much faster than conventional computers. These are simply theoretical at the mo. If you remember the Cat story, something can exist in 2 states at once, called a superposition. Only when observed (I am still not clear on what observed means to quantum physicists) will it exist in one form. What if an RNA molecule was made, what are the chances it would exist in a self replicating form? Low. But if the RNA molecule existed in several forms at once it could test these forms out. Once it found the self replicating form, this would collapse the superposition and you have a cool life starting RNA molecule.

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We are geneticists and biochemists, alumni of the University of York (2009), now doing PhDs at the Universities of Cambridge, Leeds, Oxford and Vermont. We aim to bring to your attention interesting science, whether it is making headlines or not, referencing the original peer-reviewed research as often as possible.